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1. Adjuvant nab-Paclitaxel + Gemcitabine in Resected Pancreatic Ductal Adenocarcinoma: Results From a Randomized, Open-Label, Phase III Trial

Author

Margaret A. Tempero, Uwe Pelzer, Eileen M. O'Reilly, Jordan Winter, Do-Youn Oh, Chung-Pin Li, Giampaolo Tortora, Heung-Moon Chang, Charles D. Lopez, Tanios Bekaii-Saab, Andrew H. Ko, Armando Santoro, Joon Oh Park, Marcus S. Noel, Giovanni Luca Frassineti, Yan-Shen Shan, Andrew Dean, Hanno Riess, Eric Van Cutsem, Jordan Berlin, Philip Philip, Malcolm Moore, David Goldstein, Josep Tabernero, Mingyu Li, Stefano Ferrara, Yvan Le Bruchec, George Zhang, Brian Lu, Andrew V. Biankin, Michele Reni, Richard Epstein, Paul Vasey, Jeremy Shapiro, Matthew Burge, Yu Jo Chua, Marion Harris, Nick Pavlakis, Niall Tebbutt, Gerald Prager, Christian Dittrich, Friedrich Längle, Kathrin Philipp-Abbrederis, Richard Greil, Herbert Stöger, Michael Girschikofsky, Thomas Kuehr, Jean-Luc Van Laethem, Stéphanie Laurent, Neesha Dhani, Yoo Joung Ko, Scot Dowden, Petr Kavan, Mustapha Édouard Tehfe, Eugen Kubala, Milan Kohoutek, Per Pfeiffer, Mette Yilmaz, Vibeke Parner, Tapio Salminen, Leena-Maija Soveri, Eija Korkeila, Pia Osterlund, Julien Taieb, David Tougeron, Pascal Artru, François Xavier Caroli-Bosc, Rosine Guimbaud, Antony Turpin, Thomas Walter, Jean Baptiste Bachet, Volker Kunzmann, Florian Kreth, Andreas Block, Marino Venerito, Helmut Oettle, Meinolf Karthaus, Jörg Trojan, Gunnar Folprecht, Markus Lerch, Frank Kullmann, Marcel Reiser, Volker Heinemann, Marcus-Alexander Wörns, Holger Schulz, Benjamin Garlipp, Thomas Yau, Lam Stephen Chan, Balazs Juhasz, László Landherr, Tamas Pinter, György Bodoky, Zsuzsanna Kahán, Raymond McDermott, Derek Power, Luca Gianni, Salvatore Siena, Michele Milella, Alfredo Falcone, Rossana Berardi, Cinzia Bagalà, Francesco Di Costanzo, Fausto Roila, Andrea Ardizzoni, Evaristo Maiello, Silvia Fanello, Johanna Wilmink, Jan Willem de Groot, Geert Creemers, Eduardo Barroso, Tânia Rodrigues, Cristina Sarmento, Cheng Ean Chee, David Tai, Teresa Macarulla Mercade, Manuel Hidalgo Medina, Alfredo Carrato Mena, Joan Maurel Santasusana, Maria Jose Flor Oncala, Carlos Gomez Martin, Rafael Lopez, Andres Muñoz, Ruth Vera Garcia, Inmaculada Ales, Berta Laquente Sáez, Fernando Rivera, Javier Sastre, Cheng-Chung Wu, Yu-Wen Tien, De-Chuan Chan, Tsann-Long Hwang, Jeffry Evans, Jonathan Wadsley, Pippa Corrie, Andrew Biankin, Andrew Ko, Dana Cardin, Elena Chiorean, Johanna Bendell, Anne Noonan, Hedy Kindler, Nishan Fernando, Muhammad Beg, Thomas George, Marcus Noel, Noelle LoConte, Francis Arena, James Posey, Rajat Malhotra, Charles Lopez, Davendra Sohal, Robert McWilliams, Warren Brenner, Mark Womack, Rahul Seth, Renuka lyer, Nathan Bahary, Robert Marsh, Robert Ramirez, Cynthia Chua, James Reeves, Gulam Manji, Anthony El-Khoueiry, Robert Weaver, Vaibhav Sahai, Wells Messersmith, Robert Dreicer, Ahmed Zakari, Andrea Bullock, Benjamin Musher, Mitesh Borad, Edward Kim, David Bajor, Tim Huyck, Hassan Hatoum, Henry Xiong, Boris Pasche, Jill Lacy, Olugbenga Olowokure, Allen Cohn, Donald Richards, Robert Martin, Andrew Paulson, Paul Fanta, Smitha Krishnamurthi, Paul Oberstein, Jyotsna Fuloria, Institut Català de la Salut, [Tempero MA] University of California, San Francisco, Helen Diller Family Comprehensive Cancer Center, San Francisco, CA. [Pelzer U] Charité-Universitätsmedizin Berlin, Freie Universität Berlin, Humboldt-Universität zu Berlin, Berlin Institute of Health, Berlin, Germany. [O'Reilly EM] Memorial Sloan Kettering Cancer Center, New York, NY. [Winter J] Thomas Jefferson University Hospital, Philadelphia, PA. [Oh DY] Seoul National University Hospital, Cancer Research Institute, Seoul National University College of Medicine, Seoul, South Korea. Integrated Major in Innovative Medical Science, Seoul National University Graduate School, Seoul, South Korea. [Li CP] Division of Clinical Skills Training, Department of Medical Education, Taipei Veterans General Hospital, Taipei, Taiwan. Division of Gastroenterology and Hepatology, Department of Medicine, Taipei Veterans General Hospital, Taipei, Taiwan. School of Medicine, College of Medicine, National Yang Ming Chiao Tung University, Taipei, Taiwan. [Tabernero J] Vall d'Hebron Hospital Universitari, Barcelona, Spain. Vall d'Hebron Institute of Oncology (VHIO), Barcelona, Spain. IOB-Quiron, UVic-UCC, Barcelona, Spain, and Vall d'Hebron Barcelona Hospital Campus

Subjects
Cancer Research, Chemical Actions and Uses::Pharmacologic Actions::Physiological Effects of Drugs::Immunologic Factors::Adjuvants, Immunologic [CHEMICALS AND DRUGS], acciones y usos químicos::acciones farmacológicas::efectos fisiológicos de los fármacos::factores inmunitarios::adyuvantes inmunitarios [COMPUESTOS QUÍMICOS Y DROGAS], terapéutica::terapéutica::farmacoterapia::protocolos antineoplásicos::terapéutica::farmacoterapia::protocolos de quimioterapia antineoplásica combinada [TÉCNICAS Y EQUIPOS ANALÍTICOS, DIAGNÓSTICOS Y TERAPÉUTICOS], Otros calificadores::Otros calificadores::/farmacoterapia [Otros calificadores], diagnóstico::pronóstico::resultado del tratamiento [TÉCNICAS Y EQUIPOS ANALÍTICOS, DIAGNÓSTICOS Y TERAPÉUTICOS], Other subheadings::Other subheadings::/drug therapy [Other subheadings], Diagnosis::Prognosis::Treatment Outcome [ANALYTICAL, DIAGNOSTIC AND THERAPEUTIC TECHNIQUES, AND EQUIPMENT], Quimioteràpia combinada, Oncology, Adjuvants immunològics - Ús terapèutic, Therapeutics::Therapeutics::Drug Therapy::Antineoplastic Protocols::Therapeutics::Drug Therapy::Antineoplastic Combined Chemotherapy Protocols [ANALYTICAL, DIAGNOSTIC AND THERAPEUTIC TECHNIQUES, AND EQUIPMENT], neoplasias::neoplasias::neoplasias::neoplasias por localización::neoplasias del sistema digestivo::neoplasias pancreáticas::neoplasias::neoplasias por localización::carcinoma ductal pancreático [ENFERMEDADES], Pàncrees - Càncer - Tractament, Neoplasms::Neoplasms::Neoplasms::Neoplasms by Site::Digestive System Neoplasms::Pancreatic Neoplasms::Neoplasms::Neoplasms by Site::Carcinoma, Pancreatic Ductal [DISEASES], APACT Investigators
Abstract

PURPOSE This randomized, open-label trial compared the efficacy and safety of adjuvant nab-paclitaxel + gemcitabine with those of gemcitabine for resected pancreatic ductal adenocarcinoma (ClinicalTrials.gov identifier: NCT01964430 ). METHODS We assigned 866 treatment-naive patients with pancreatic ductal adenocarcinoma to nab-paclitaxel (125 mg/m2) + gemcitabine (1,000 mg/m2) or gemcitabine alone to one 30-40 infusion on days 1, 8, and 15 of six 28-day cycles. The primary end point was independently assessed disease-free survival (DFS). Additional end points included investigator-assessed DFS, overall survival (OS), and safety. RESULTS Two hundred eighty-seven of 432 patients and 310 of 434 patients completed nab-paclitaxel + gemcitabine and gemcitabine treatment, respectively. At primary data cutoff (December 31, 2018; median follow-up, 38.5 [interquartile range [IQR], 33.8-43 months), the median independently assessed DFS was 19.4 ( nab-paclitaxel + gemcitabine) versus 18.8 months (gemcitabine; hazard ratio [HR], 0.88; 95% CI, 0.729 to 1.063; P = .18). The median investigator-assessed DFS was 16.6 (IQR, 8.4-47.0) and 13.7 (IQR, 8.3-44.1) months, respectively (HR, 0.82; 95% CI, 0.694 to 0.965; P = .02). The median OS (427 events; 68% mature) was 40.5 (IQR, 20.7 to not reached) and 36.2 (IQR, 17.7-53.3) months, respectively (HR, 0.82; 95% CI, 0.680 to 0.996; P = .045). At a 16-month follow-up (cutoff, April 3, 2020; median follow-up, 51.4 months [IQR, 47.0-57.0]), the median OS (511 events; 81% mature) was 41.8 ( nab-paclitaxel + gemcitabine) versus 37.7 months (gemcitabine; HR, 0.82; 95% CI, 0.687 to 0.973; P = .0232). At the 5-year follow-up (cutoff, April 9, 2021; median follow-up, 63.2 months [IQR, 60.1-68.7]), the median OS (555 events; 88% mature) was 41.8 versus 37.7 months, respectively (HR, 0.80; 95% CI, 0.678 to 0.947; P = .0091). Eighty-six percent ( nab-paclitaxel + gemcitabine) and 68% (gemcitabine) of patients experienced grade ≥ 3 treatment-emergent adverse events. Two patients per study arm died of treatment-emergent adverse events. CONCLUSION The primary end point (independently assessed DFS) was not met despite favorable OS seen with nab-paclitaxel + gemcitabine.

Published
2023

2. Dipeptide metabolite, glutamyl-glutamate mediates microbe-host interaction to boost spermatogenesis

Author

Balázs Juhász, Krisztina Horváth, Dániel Kuti, Jian Shen, Annette Feuchtinger, Chaoyang Zhang, Ildikó Bata-Vidács, István Nagy, József Kukolya, Michael Witting, Mária Baranyi, Szilamér Ferenczi, Axel Walch, Na Sun, and Krisztina J. Kovács

Subjects
Medicine, Science
Abstract

Abstract The decrease in sperm count and infertility is a global issue that remains unresolved. By screening environmental bacterial isolates, we have found that a novel lactic acid bacterium, Lactiplantibacillus plantarum SNI3, increased testis size, testosterone levels, sperm count, sexual activity and fertility in mice that have consumed the bacteria for four weeks. The abundance of L. plantarum in the colon microbiome was positively associated with sperm count. Fecal microbiota transplantation (FMT) from L. plantarum SNI3-dosed mice improved testicular functions in microbiome-attenuated recipient animals. To identify mediators that confer pro-reproductive effects on the host, untargeted in situ mass spectrometry metabolomics was performed on testis samples of L. plantarum SNI3-treated and control mice. Enrichment pathway analysis revealed several perturbed metabolic pathways in the testis of treated mice. Within the testis, a dipeptide, glutamyl-glutamate (GluGlu) was the most upregulated metabolite following L. plantarum SNI3 administration. To validate the pro-reproductive feature of GluGlu, systemic and local injections of the dipeptide have been performed. γ-GluGlu increased sperm count but had no effect on testosterone. These findings highlight the role of γ-GluGlu in mediating spermatogenetic effects of L. plantarum on the male mouse host and –following relevant human clinical trials- may provide future tools for treating certain forms of male infertility.

Published
2024
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3. Impact of Neoadjuvant Sunitinib Treatment on Tumour Thrombi in the Inferior Vena Cava in Metastatic Renal Cell Carcinoma

Author

Tibor Flaskó, Csaba Berczi, Balazs Juhasz, Akos Berczi, and Tamás Szerafin

Subjects
Cultural Studies, medicine.medical_specialty, lcsh:Internal medicine, lcsh:Specialties of internal medicine, metastatic renal cancer, lcsh:Medicine, urologic and male genital diseases, lcsh:RC870-923, Inferior vena cava, lcsh:RC254-282, Renal cell carcinoma, lcsh:RC581-951, medicine, cardiovascular diseases, lcsh:RC31-1245, neoadjuvant sunitinib, tumour thrombus, Sunitinib, business.industry, lcsh:R, Religious studies, medicine.disease, lcsh:Diseases of the genitourinary system. Urology, lcsh:Neoplasms. Tumors. Oncology. Including cancer and carcinogens, medicine.vein, cardiovascular system, Radiology, business, inferior vena cava, medicine.drug, radical nephrectomy
Abstract

The authors report cases of metastatic renal cell carcinoma with level III-IV tumour thrombi in the inferior vena cava (IVC). Cases were treated with three courses of neoadjuvant sunitinib to reduce the thrombus level before surgery. Nephrectomy and tumour thrombectomy were performed, and sunitinib treatment continued after the operation. Cases 1 and 3 showed regression of lung metastases, but the size of the primary renal tumour and thrombus remained the same. The progression-free survival of the cases was 35 months and 24 months, respectively. In case 2, the primary renal tumour, metastases and thrombus showed regression. The upper limit of the thrombus decreased by 3 cm. In this case, the progression-free survival was 15 months, and the cancer-specific survival was 18 months. The neoadjuvant sunitinib treatment had a limited effect on downsizing the extent of tumour thrombi in the IVC.

Published
2020

4. Preliminary safety and efficacy of first-line pertuzumab combined with trastuzumab and taxane therapy for HER2-positive locally recurrent or metastatic breast cancer (PERUSE)

Author

T. Bachelot, E. Ciruelos, A. Schneeweiss, F. Puglisi, T. Peretz-Yablonski, I. Bondarenko, S. Paluch-Shimon, A. Wardley, J.-L. Merot, Y. du Toit, V. Easton, N. Lindegger, D. Miles, Kamel Bouzid, Mario Campone, Bruno Coudert, Zbigniew Nowecki, Hassan Errihani, Florence Dalenc, Ana Ferreira, Max Mano, Francesco Ricci, Haralabos Kalofonos, Claudia Andreetta, Filippo Montemurro, Sophie Barrett, Qingyuan Zhang, Dimitris Mavroudis, Juan Matus, Carlos Beato, Xichun Hu, Rabab Gaafar, Hamdy Abdel Azeem, Christophe Perrin, Johannes Ettl, Istvan Lang, Sunil Verma, Huiping Li, Etienne Brain, Oliver Hoffmann, Anna Cariello, Carlo Tondini, Taher Altwegeiri, Niklas Loman, Michael Lux, Antonio Frassoldati, Zeba Aziz, Fernando Salas, Joanna Streb, Andrzej Wronski, Salomón Menjón Beltrán, Irfan Cicin, Peter Schmid, Robert Laing, Zhongsheng Tong, Katalin Boer, Balazs Juhasz, Luca Gianni, Giuseppe Curigliano, Alejandro Juarez, Snezana Susnjar, Erika Matos, Ruchan Uslu, Hans Wildiers, Marcelo Cruz, Hugues Bourgeois, Raquel von Schumann, Salomón Stemmer, Flavia Morales Vásquez, Adriana Dominguez, Marek Wojtukiewicz, Jasna Trifunovic, Jose Juan Illarramendi, Laura Garcia, Yann Izarzugaza Peron, Maria Jose Echarri, Natliia Voitko, Duncan Wheatley, Simon Waters, Richard De Boer, Guy Jerusalem, Véronique Cocquyt, Carlos Barrios, Lawrence Panasci, Johanna Mattson, Minna Tanner, Michel Gozy, Georgios Vasilopoulos, Janos Revesz, Luciano Latini, Cesare Gridelli, Jesus Lazaro, Antonio Gonzalez, Agusti Barnadas Molins, Eduardo Martinez, Jesús Alarcón, Ana Arance, Leif Klint, Oleksiy Kovalyov, Richard Baird, Belinda Yeo, Nicole McCarthy, Richard Greil, Shusen Wang, Xavier Artignan, Paule Augereau, Ingolf Juhasz-Boess, Roger Ngan, Hadassah Goldberg, Francesco Di Costanzo, Francesco Ferraù, Eduardas Aleknavicius, Kamran Rashid, Luís Costa, Jose Angel Garcia, Luis Ruiz de la Cruz, Rafael López López, Olga Del Val, Ozgur Ozyilkan, Fathi Azribi, Mark Verrill, Nicholas Turner, Jane Beith, Andreas Petzer, Jurandyr Andrade, Vanessa Bernstein, Daniel Rayson, Ibtessam Saad Eldin, Mihaëla Achille, Volkmar Mueller, Alessandra Gennari, Stefano Cascinu, Marwan Ghosn, Nagi El-Saghir, Joan Van den Bosch, Rianne Oosterkamp, Monika Kukulska, Ignacio Pelaez, Carolina Hernandez, Maria del Mar Gordon, Elsa Dalmau, Jose Luis Alonso, Sercan Aksoy, Hasan Senol Coskun, Yaroslav Shparyk, Mohini Varughese, Udaiveer Panwar, Lisa Barraclough, Nicola Levitt, Jonathan Hicks, Anna Rigg, Mark Allen, Cecila Castillo, Luis Enrique Fein, Robin Stuart-Harris, Christian Singer, Herbert Stoeger, Sasha Smiljanic, Jifeng Feng, Miguel Cedeño, Jean Francois Berdah, Hubert Orfeuvre, Anthony Goncalves, Eva-Maria Grischke, Eike Simon, Steffen Wagner, Anna Efremidou, Konstantinos Papazisis, Ella Evron, Moshe Inbar, Noa Ben Baruch, David Geffen, Natalya Karminsky, Enzo Maria Ruggeri, Cavanna Luigi, Donatella Grasso, Elona Juozaityte, Jeronimo Rafael Rodriguez Cid, Henk Roerdink, Neelum Siddiqi, José Luís Passos Coelho, Elisa Garcia Garre, Andres Garcia, Noelia Martínez Jañez, Maria Helena Lopez Ceballos, Mireia Mele, María García, Alberto Arcediano, Karen McAdam, Timothy Perren, Wendy Taylor, Alison Humphreys, Raul Vera, Luis Alberto Kaen, Günther Steger, Johannes Andel, Jacques de Grève, Manon Huizing, Roberto Hegg, Anil Joy, Sandeep Sehdev, Riina Kütner, Johanna Ruohola, Nadine Dohollou, Jessica Grosjean, Philippe Laplaige, Rémy Largillier, Philippe Martin, Virginie Pottier, Jerome Alexandre, Bernd Christensen, Dirk-Michael Zahm, Fariba Khandan, Hans-Joachim Lueck, Georgios Fountzilas, Georgeta Fried, Alice Giacobino, Andrea Bonetti, Yanin Chavarri Guerra, Laurens Van Warmerdam, Annette Van der Velden, Suzan Vrijaldenhoven, Felix de Jongh, Milagros Cavero, Raquel Andres Conejero, Adolfo Murias, Salvador Saura, Amparo Oltra, Andres Redondo, Nuria Ribelles, Kilian Bachmeier, Johnathan Joffe, Prabir Chakraborti, Mark Beresford, Mohammad Butt, Christopher Poole, Gassan Yordi, Natasha Woodward, Gilberto Amorim, Nadia Califaretti, Susan Fox, Andre Robidoux, NanLi Li, Nenxiao Li, Jun Jiang, Tannia Soria, Peeter Padrik, Outi Saarni, Dominique Genet, Stéphanie Catala, Hugues Barletta, Luis Teixeira, Thomas Facchini, Tobias Hesse, Thorsten Kühn, Angelika Ober, Roland Repp, Willibald Schroeder, Dimitrios Pectasides, Gyorgy Bodoky, Zsuzsanna Kahan, Irina Jiveliouk, Ora Rosengarten, Oscar Alabiso, Mario Perez, Yes Van de Wouw, Jolanta Smok-Kalwat, Margarida Damasceno, Gabriela Sousa, Omalkhair Abulkhair, Antonio Antón Torres, Maria Purificación Martinez, Jesús Garcia Mata, Marta Santisteban Jesús Florián Jerico, Antonio Llombart, Rosa Sanchez, Juan Carlos Torrego, Clara Olier Garate, Cesar Rodriguez, Rosa Llorente, Diego Soto de Prado, Javier Cortés, Cristina Llorca, Antonio Galán, Gemma Viñas Villaro, Ulrik Narbe, Helena Granstam Bjömeklett, Sarah Westwell, Jackie Newby, Mariam Jafri, Robinson Rodríguez, Isabel Alonso, Medical Genetics, Clinical sciences, and Laboratory for Medical and Molecular Oncology

Subjects
0301 basic medicine, Oncology, Male, Receptor, ErbB-2, first line, chemistry.chemical_compound, 0302 clinical medicine, dual HER2 blockade, Trastuzumab, Antineoplastic Combined Chemotherapy Protocols, Prospective Studies, Neoplasm Metastasis, skin and connective tissue diseases, Aged, 80 and over, Medicine(all), Hematology, Middle Aged, Metastatic breast cancer, Survival Rate, Docetaxel, Paclitaxel, 030220 oncology & carcinogenesis, Female, Taxoids, Pertuzumab, metastatic breast cancer, medicine.drug, Adult, Bridged-Ring Compounds, medicine.medical_specialty, HER2-positive, paclitaxel, pertuzumab, Breast Neoplasms, Antibodies, Monoclonal, Humanized, Loading dose, Breast Neoplasms, Male, 03 medical and health sciences, Young Adult, Internal medicine, medicine, Biomarkers, Tumor, Humans, neoplasms, Aged, Neoplasm Staging, Taxane, business.industry, medicine.disease, 030104 developmental biology, chemistry, Neoplasm Recurrence, Local, business, Febrile neutropenia
Abstract

Background Pertuzumab combined with trastuzumab and docetaxel is the standard first-line therapy for HER2-positive metastatic breast cancer, based on results from the phase III CLEOPATRA trial. PERUSE was designed to assess the safety and efficacy of investigator-selected taxane with pertuzumab and trastuzumab in this setting. Patients and methods In the ongoing multicentre single-arm phase IIIb PERUSE study, patients with inoperable HER2-positive advanced breast cancer (locally recurrent/metastatic) (LR/MBC) and no prior systemic therapy for LR/MBC (except endocrine therapy) received docetaxel, paclitaxel or nab-paclitaxel with trastuzumab [8mg/kg loading dose, then 6mg/kg every 3weeks (q3w)] and pertuzumab (840mg loading dose, then 420mg q3w) until disease progression or unacceptable toxicity. The primary end point was safety. Secondary end points included overall response rate (ORR) and progression-free survival (PFS). Results Overall, 1436 patients received at least one treatment dose (initially docetaxel in 775 patients, paclitaxel in 589, nab-paclitaxel in 65; 7 discontinued before starting taxane). Median age was 54years; 29% had received prior trastuzumab. Median treatment duration was 16months for pertuzumab and trastuzumab and 4months for taxane. Compared with docetaxel-containing therapy, paclitaxel-containing therapy was associated with more neuropathy (all-grade peripheral neuropathy 31% versus 16%) but less febrile neutropenia (1% versus 11%) and mucositis (14% versus 25%). At this preliminary analysis (52 months' median follow-up), median PFS was 20.6 [95% confidence interval (CI) 18.9–22.7] months overall (19.6, 23.0 and 18.1months with docetaxel, paclitaxel and nab-paclitaxel, respectively). ORR was 80% (95% CI 78%–82%) overall (docetaxel 79%, paclitaxel 83%, nab-paclitaxel 77%). Conclusions Preliminary findings from PERUSE suggest that the safety and efficacy of first-line pertuzumab, trastuzumab and taxane for HER2-positive LR/MBC are consistent with results from CLEOPATRA. Paclitaxel appears to be a valid alternative taxane backbone to docetaxel, offering similar PFS and ORR with a predictable safety profile. ClinicalTrials.gov NCT01572038.

Published
2019

5. Associations of vascular and bone status in arthritis patients

Author

Anita Pusztai, Attila Hamar, Monika Czókolyová, Katalin Gulyás, Ágnes Horváth, Edit Végh, Zsófia Pethő, Szilvia Szamosi, Emese Balogh, Nóra Bodnár, Levente Bodoki, Ágnes Szentpétery, Harjit Pal Bhattoa, György Kerekes, Balázs Juhász, Éva Szekanecz, Katalin Hodosi, Andrea Domján, Sándor Szántó, Hennie G. Raterman, Willem F. Lems, Zoltán Szekanecz, and Gabriella Szűcs

Subjects
Medicine, Science
Abstract

Abstract Cardiovascular (CV) disease and osteoporosis (OP) have been associated with rheumatoid arthritis (RA) and ankylosing spondylitis (AS). Bone and vascular biomarkers and parameters along with the effect of 1-year anti-TNF therapy on these markers were assessed in order to determine correlations between vascular pathophysiology and bone metabolism in RA and AS. Thirty-six patients treated with etanercept or certolizumab pegol and 17 AS patients treated with ETN were included in a 12-month follow-up study. Bone and vascular markers were previously assessed by ELISA. Bone density was measured by DXA and quantitative CT (QCT). Flow-mediated vasodilation (FMD), common carotid intima-media thickness (IMT) and pulse-wave velocity (PWV) were assessed by ultrasound. Multiple correlation analyses indicated associations between bone and vascular markers. Osteoprotegerin, sclerostin and cathepsin K were significantly associated with FMD, IMT and PWV, respectively (p

Published
2021
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6. Peripheral quantitative computed tomography in the assessment of bone mineral density in anti-TNF-treated rheumatoid arthritis and ankylosing spondylitis patients

Author

Balázs Juhász, Katalin Gulyás, Ágnes Horváth, Edit Végh, Anita Pusztai, Ágnes Szentpétery, Zsófia Pethő, Nóra Bodnár, Attila Hamar, Levente Bodoki, Harjit Pal Bhattoa, Éva Szekanecz, Katalin Hodosi, Andrea Domján, Szilvia Szamosi, Csaba Horváth, Sándor Szántó, Gabriella Szűcs, Hennie G. Raterman, Willem F. Lems, Oliver FitzGerald, and Zoltán Szekanecz

Subjects
Rheumatoid arthritis, Ankylosing spondylitis, Osteoporosis, Bone density, Peripheral quantitative computed tomography, Biologics, Diseases of the musculoskeletal system, RC925-935
Abstract

Abstract Introduction Rheumatoid arthritis (RA) and ankylosing spondylitis (AS) are associated with osteoporosis. There have not been many peripheral quantitative computed tomography (QCT) studies in patients receiving biologics. We assessed volumetric and areal bone mineral density (BMD) by forearm QCT and dual-energy X-ray absorptiometry (DXA), respectively in addition to laboratory biomarkers in these arthritides. Methods Forty RA and AS patients treated with either etanercept (ETN) or certolizumab pegol (CZP) were undergoing follow-ups for one year. Volumetric and areal BMD, as well as parathyroid hormone (PTH), osteocalcin, RANKL, 25-hydroxyvitamin D (VITD), P1NP, CTX, sclerostin (SOST), Dickkopf 1 (DKK-1) and cathepsin K (CATHK) were determined. Results We did not observe any further bone loss during the 12-month treatment period. Volumetric and areal BMD showed significant correlations with each other (p

Published
2021
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7. Efficient treatment of a preclinical inflammatory bowel disease model with engineered bacteria

Author

Szilamer Ferenczi, Norbert Solymosi, István Horváth, Natália Szeőcs, Zsuzsanna Grózer, Dániel Kuti, Balázs Juhász, Zsuzsanna Winkler, Tibor Pankotai, Farkas Sükösd, Anikó Stágel, Melinda Paholcsek, Dávid Dóra, Nándor Nagy, Krisztina J. Kovács, Ivan Zanoni, and Zoltan Szallasi

Subjects
RNA interference, engineered E. coli, treatment of ulcerative colitis, bacterial therapeutic delivery, Genetics, QH426-470, Cytology, QH573-671
Abstract

We developed an orally administered, engineered, bacterium-based, RNA interference-mediated therapeutic method to significantly reduce the symptoms in the most frequently used animal model of inflammatory bowel disease. This bacterium-mediated RNA interference strategy was based on the genomically stable, non-pathogenic E. coli MDS42 strain, which was engineered to constitutively produce invasin and the listeriolysin O cytolysin. These proteins enabled the bacteria first to invade the colon epithelium and then degrade in the phagosome. This allowed the delivery of a plasmid encoding small hairpin RNA (shRNA) targeting tumor necrosis factor (TNF) into the cytoplasm of the target cells. The expression levels of TNF and other cytokines significantly decreased upon this treatment in dextran sulfate sodium (DSS)-induced colitis, and the degree of inflammation was significantly reduced. With further safety modifications this method could serve as a safe and side effect-free alternative to biologicals targeting TNF or other inflammatory mediators.

Published
2021
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8. The metabolic stress response: Adaptation to acute-, repeated- and chronic challenges in mice

Author

Dániel Kuti, Zsuzsanna Winkler, Krisztina Horváth, Balázs Juhász, Anett Szilvásy-Szabó, Csaba Fekete, Szilamér Ferenczi, and Krisztina J. Kovács

Subjects
Biological sciences, Physiology, Immunology, Science
Abstract

Summary: There is a strong relationship between stress and metabolism. Because acute traumatic- and chronic stress events are often accompanied with metabolic pathophysiology, it is important to understand the details of the metabolic stress response. In this study we directly compared metabolic effects of acute stress with chronic repeated- and chronic unpredictable stress in mouse models. All types of adversities increased energy expenditure, chronic stress exposure decreased body weight gain, locomotor activity and differentially affected fuel utilization. During chronic exposure to variable stressors, carbohydrates were the predominant fuels, whereas fatty acids were catabolized in acutely and repeatedly restrained animals. Chronic exposure to variable stressors in unpredictable manner provoked anxiety. Our data highlight differences in metabolic responses to acute- repeated- and chronic stressors, which might affect coping behavior and underlie stress-induced metabolic and psychopathologies.

Published
2022
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9. Carità pelosa. Gli aiuti italiani all’Ungheria post-asburgica

Author

Balazs Juhász

Subjects
History (General) and history of Europe, Military Science
Abstract

Humanitarian aid as it is meant today (i.e. transnationally-coordinated, state-subsidized and carried out by volunteers), first came into being during WWI and its aftermath. Relief actions carried out by the Entente powers in the countries of the former Central Empires averted an humanitarian disaster but were also a mean to further politic and economic agendas. This paper focuses on the assistance that Italy gave to Hungary in 1919-1920 as a possible early attempt at economic expansion in that country.

Published
2020
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10. La fuga dei prigionieri austro-ungarici dai campi italiani tra percezione e problemi reali

Author

Balazs Juhász

Subjects
History (General) and history of Europe, Military Science
Abstract

The escape of prisoners of war is a personal experience, not measurable with statistics only, as the decision to flee is, partly at least, irrational and/or due to the prisoner’s subjective perception of captivity. This paper examines the extraordinarily well documented case of the attempted escape by an Austro-Hungarian officer in 1916, trying to discover what moved prisoners to escape, how this phenomenon was managed by Italian authorities and judged by the general public.

Published
2020
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11. Complex assessment of bone mineral density, fracture risk, vitamin D status, and bone metabolism in Hungarian systemic sclerosis patients

Author

Ágnes Horváth, Edit Végh, Anita Pusztai, Zsófia Pethő, Attila Hamar, Monika Czókolyová, Harjit Pal Bhattoa, Gábor Nagy, Balázs Juhász, Katalin Hodosi, Andrea Domján, Zoltán Szekanecz, Gabriella Szücs, and Szilvia Szamosi

Subjects
Systemic sclerosis, Bone loss, Osteoporosis, DXA, pQCT, Pulmonary manifestations, Diseases of the musculoskeletal system, RC925-935
Abstract

Abstract Objective We wished to determine bone alterations in systemic sclerosis (SSc) patients by conventional densitometry (DXA), peripheral quantitative computed tomography (pQCT), and bone biomarkers. Methods We included 44 SSc patients and 33 age-matched healthy controls. Lumbar spine and femoral neck bone mineral density (BMD) was assessed by DXA. Volumetric BMD was measured by pQCT at the radius. FRAX, 25-hydroxyvitamin-D3 (25-OH-D3), parathyroid hormone, osteocalcin, C-terminal collagen telopeptide, and procollagen type I amino-terminal propeptide were also assessed. Results SSc patients had lower L2–4 BMD (0.880 ± 0.108 vs. 0.996 ± 0.181 g/cm2; p = 0.019) and femoral neck (FN) BMD (0.786 ± 0.134 vs. 0.910 ± 0.090 g/cm2; p = 0.007) by DXA. In SSc vs. controls, pQCT indicated lower mean cortical (328.03 ± 103.32 vs. 487.06 ± 42.45 mg/cm3; p

Published
2019
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